Adamu Shittu Muhammad, Oyewole Olaoye Stephen, Kabir Umar Farouk
Department of Obstetrics and Gynaecology, Federal Medical Centre Gusau, Zamfara State, Nigeria.
Department of Radiology, Usman Danfodiyo University Teaching Hospital, Sokoto, Sokoto State, Nigeria.
Niger Med J. 2024 Apr 21;65(1):1-15. doi: 10.60787/nmj-v65i1-447. eCollection 2024 Jan-Feb.
Platinum-based chemotherapy after surgical cytoreduction is the universal treatment for advanced ovarian cancer (OC), however, about eighty percent of patients experienced relapse and progression-free survival remained poor. Patients who relapsed within one year of treatment eventually become resistant to second-line chemotherapy. Poly-ADP-ribose polymerase inhibitors are a novel class of targeted therapy that could overcome these challenges by augmenting the chemotherapeutic activity of other cytotoxic agents. Cumulative Index to Nursing and Allied Health Literature (CINHAL), Cochrane and PubMed databases were searched for potentially relevant primary publications from 2011 to 2022 reporting on efficacy and safety of combination of a PARP inhibitor and chemotherapy versus chemotherapy in recurrent OC and reviewed. The outcomes of interest assessed qualitatively were progression-free survival (PFS) and grade 3 or higher adverse events (AEs) as measures of efficacy and safety respectively. Eight randomized controlled trials (RCTs) were included in the systematic review comprising 3,021 patients evaluated efficacy and safety of PARP inhibitors: Olaparib, niraparib and veliparib with combinations of bevacizumab, carboplatin, cisplatin, cediranib, cyclophosphamide and paclitaxel. 824 patients had 33 BRCA mutation while 1,430 had wild-type BRCA, an allele that confers increased risk of cancer. Most patients had platinum-sensitive cancers. There was significant prolongation of PFS with PARP inhibitor and chemotherapy combination compared to chemotherapy in all included trials except one which combined veliparib with cyclophosphamide. The prolongation of PFS was more remarkable in patients with BRCA mutation and occasionally patients with wild-type BRCA. Niraparib and veliparib were notably associated with grade 3 or higher anaemia, neutropenia, and thrombocytopenia, olaparib caused fatigue and gastrointestinal disturbances while bevacizumab and cediranib caused hypertension. This review suggested combined PARP inhibitor and chemotherapy significantly prolonged progression-free survival especially in patients with BRCA mutation compared to chemotherapy and the combined therapy is safe.
手术细胞减灭术后的铂类化疗是晚期卵巢癌（OC）的通用治疗方法，然而，约80%的患者会复发，无进展生存期仍然较差。在治疗一年内复发的患者最终会对二线化疗产生耐药性。聚ADP核糖聚合酶抑制剂是一类新型靶向治疗药物，可通过增强其他细胞毒性药物的化疗活性来克服这些挑战。检索了护理及联合健康文献累积索引（CINHAL）、考科蓝数据库和PubMed数据库，以查找2011年至2022年期间报告PARP抑制剂与化疗联合应用与化疗在复发性OC中的疗效和安全性的潜在相关主要出版物，并进行综述。定性评估的感兴趣结局分别是无进展生存期（PFS）和3级或更高等级不良事件（AE），作为疗效和安全性的衡量指标。系统评价纳入了8项随机对照试验（RCT），共3021例患者，评估了PARP抑制剂（奥拉帕利、尼拉帕利和维利帕利）与贝伐单抗、卡铂、顺铂、西地尼布、环磷酰胺和紫杉醇联合应用的疗效和安全性。824例患者有33个BRCA突变，1430例有野生型BRCA（一种增加癌症风险的等位基因）。大多数患者患有铂敏感型癌症。除一项将维利帕利与环磷酰胺联合应用的试验外，在所有纳入试验中，与化疗相比，PARP抑制剂与化疗联合应用可显著延长PFS。BRCA突变患者和偶尔的野生型BRCA患者的PFS延长更为显著。尼拉帕利和维利帕利与3级或更高等级的贫血、中性粒细胞减少和血小板减少显著相关，奥拉帕利导致疲劳和胃肠道不适，而贝伐单抗和西地尼布导致高血压。该综述表明，与化疗相比，PARP抑制剂与化疗联合应用可显著延长无进展生存期，尤其是BRCA突变患者，且联合治疗是安全的。
